Optimization of alginate encapsulation of islets for transplantation

Abstract

Apparatus is provided, including a plurality of islets, and a hydrogel configured to macroencapsulate the plurality of islets. The hydrogel is implantable in a subcapsular space ( 21 ) of a kidney ( 22 ) of a subject and is shaped to define a planar configuration. Other applications are also described.

The invention claimed is: 
     
       1. A method for controlling the blood glucose levels in a subject in need thereof, comprising:
 a. providing an implantable device having pancreatic islets containing insulin-producing cells in an amount sufficient to maintain blood glucose levels at a normal level in the subject, macroencapsulated in a three dimensional hydrogel, wherein the three dimensional hydrogel has a planar configuration and has a thickness from 300 microns to 500 microns wherein the amount sufficient to maintain blood glucose levels at a normal level in the subject is a density from 27,000 islets/cm 3  to 43,750 islets/cm 3 ; and 
 b. implanting the implantable device in the subject,
 wherein following implantation, the implantable device maintains blood glucose levels at a normal level in the subject for at least 20 days. 
 
 
     
     
       2. The method according to  claim 1 , wherein the three dimensional hydrogel is covered at least in part by a semi-permeable membrane. 
     
     
       3. The method according to  claim 1 , wherein the pancreatic islets containing insulin-producing cells are provided in three-dimensional hydrogel and in a semi-permeable membrane that is disposed at least in part within the three-dimensional hydrogel. 
     
     
       4. The method according to  claim 1 , wherein the implantable device is implanted in the subcapsular space of the kidney. 
     
     
       5. The method according to  claim 4 , further comprising removing the implantable device from the subcapsular space of the kidney using laparoscopy. 
     
     
       6. The method according to  claim 1 , wherein the three dimensional hydrogel comprises constituents of extracellular matrix. 
     
     
       7. The method according to  claim 1 , wherein the three dimensional hydrogel comprises collagen. 
     
     
       8. The method according to  claim 1 , wherein the three dimensional hydrogel comprises laminin. 
     
     
       9. The method according to  claim 1 , wherein the three dimensional hydrogel comprises alginate having a concentration of guluronic acid of between 30% and 50%. 
     
     
       10. The method according to  claim 9 , wherein the alginate comprises alginate having a concentration of guluronic acid of between 40% and 47%. 
     
     
       11. The method according to  claim 9 , wherein the alginate comprises alginate having a dry matter content of at least 1.6%. 
     
     
       12. The method according to  claim 9 , wherein the alginate comprises alginate having a dry matter content of at least 2.1%. 
     
     
       13. The method according to  claim 9 , wherein the alginate comprises alginate that is cross-linked with strontium. 
     
     
       14. The method according to  claim 12 , wherein the alginate comprises alginate having a dry matter content of between 2.1% and 5.0%. 
     
     
       15. The method according to  claim 1 , wherein implanting comprises implanting the implantable device in an area of a body of the subject selected from the group consisting of: a subcapsular space of a kidney of the subject, a liver of the subject, an area in a vicinity of a diaphragm of the subject, and an omental pouch of the subject. 
     
     
       16. The method according to  claim 9 , wherein the alginate comprises alginate that is cross-linked with barium.